ENDOKRIN dr Jimmy H W Sp PA ENDOKRIN

ENDOKRIN dr. Jimmy H. W. , Sp. PA

ENDOKRIN • Kelenjar mengeluarkan hormon

Figure 24 -1 Hormones released by the anterior pituitary. The adenohypophysis (anterior pituitary) releases five hormones that are in turn under the control of various stimulatory and inhibitory hypothalamic releasing factors. TSH, thyroid-stimulating hormone (thyrotropin); PRL, prolactin; ACTH, adrenocorticotrophic hormone (corticotropin); GH, growth hormone (somatotropin); FSH, follicle-stimulating hormone; LH, luteinizing hormone. The stimulatory releasing factors are TRH (thyrotropin-releasing factor), CRH (corticotropin-releasing factor), GHRH (growth hormone-releasing factor), Gn. RH (gonadotropin-releasing factor). The inhibitory hypothalamic influences are comprised of PIF (prolactin inhibitory factor or dopamine) and growth hormone inhibitory factor (GIH or somatostatin). Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03: 46 AM) © 2005 Elsevier

Kelenjar Hipofise ( Pituitary ) • 1 cm, 0, 5 gr, pada sella tursica • Jenis hormon : 1. Adenohipofise FSH PRL - GH - TSH - 2. Neurohipofise Oksitosin Vasopresin ADH ACTHLH

Figure 24 -7 Homeostasis in the hypothalamus-pituitary-thyroid axis and mechanism of action of thyroid hormones. Secretion of thyroid hormones (T 3 and T 4) is controlled by trophic factors secreted by both the hypothalamus and the anterior pituitary. Decreased levels of T 3 and T 4 stimulate the release of thyrotropin-releasing hormone (TRH) from the hypothalamus and thyroid-stimulating hormone (TSH) from the anterior pituitary, causing T 3 and T 4 levels to rise. Elevated T 3 and T 4 levels, in turn, suppress the secretion of both TRH and TSH. This relationship is termed a negative-feedback loop. TSH binds to the TSH receptor on the thyroid follicular epithelium, which causes activation of G proteins, and cyclic AMP (c. AMP)-mediated synthesis and release of thyroid hormones (T 3 and T 4). In the periphery, T 3 and T 4 interact with the thyroid hormone receptor (TR) to form a hormone-receptor complex that translocates to the nucleus and binds to so-called thyroid response elements (TREs) on target genes initiating transcription. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03: 46 AM) © 2005 Elsevier

Hiperpituitarism Oleh karena : § Adenoma § Hiperplasia § Carcinoma § Kelainan Hipotalamus

ADENOMA HIPOFISE : • 10 % tumor otak • Usia 30 – 50 tahun • Satu jenis tumor 1 jenis hormon Makroskopis : • Batas jelas, lunak • Kecil (mm) – besar (cm) • Lesi besar invasive adenoma • Perdarahan apoplexi

Mikroskopis : • Sel uniform, poligonal, jalur/lembaran • Jaringan ikat penyangga • Inti uniform – pleomorfik

Klinik : • Rö bayangan pada sella tursica ekspansi sellar erosi tulang kerusakan diafragma • Gangguan produksi hipopituitarisme • Penekanan tumor gangguan chiasmo opticum (bitemporal hemianopsi) • Tekanan intracranial naik ü Pusing ü Mual/muntah

Figure 24 -4 Pituitary adenoma. This massive, nonfunctional adenoma has grown far beyond the confines of the sella turcica and has distorted the overlying brain. Nonfunctional adenomas tend to be larger at the time of diagnosis than those that secrete a hormone. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03: 46 AM) © 2005 Elsevier

Figure 24 -4 Pituitary adenoma. This massive, nonfunctional adenoma has grown far beyond the confines of the sella turcica and has distorted the overlying brain. Nonfunctional adenomas tend to be larger at the time of diagnosis than those that secrete a hormone. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03: 46 AM) © 2005 Elsevier

PROLAKTINOMA • • Tumor hipofise terbanyak ( 30 % ) Usia 20 – 40 th, pria > wanita Mikro atau makro Efek dari tumor PRL naik galactorrhea libido kurang infertil amenorrhea

PROLAKTINOMA Prolaktin tinggi juga karena : • Hamil • Stress • Hiperplasi sel laktotrof

PROLAKTINOMA Hiperplasi sel laktotrof karena : • Hipotalamus rusak neuron dopaminergik rusak • Obat yang menekan reseptor dopamin pada hipofise phenotiazin reserpin haloperidol

PROLAKTINOMA Terapi : • Bromocriptin sebagai antagonist receptor dopamin

Hipopituitarisme, karena : Faktor Hipofise : • Tumor non fungsionil / kista • Operasi / radiasi • Ischemic necrosis/post partum necrosis (Sheehan syndrome) • Empty sella syndrome • Genetik

Faktor Hipotalamus : • Tumor primer / sekunder • Infeksi / degenerasi Klinik hipopituitarisme : 1. Fungsi kelenjar perifer turun • Adrenal • Thyroid • Gonad 2. Wajah pucat MSH rendah 3. Atrofi genitalia

Hipofise posterior • Hormon produksi – ADH – Oksitosin • Diabetes insipidus – ADH rendah – Etiologi : trauma, infeksi, tumor – Klinik : haus urine banyak Na serum tinggi, osmositas

• Syndrome of Inappropriate ADH secretion : – ADH tinggi – Etiologi : Ca small cell paru-paru – Klinik : urine sedikit Na serum rendah

Tumor Hipotalamus • Glioma • Craniopharyngioma

Craniopharyngioma • Dari : Vestigical Remnants Rathke Pouch • Usia : anak – dewasa muda • Morfologi : – Umumnya jinak – Soliter, kistik, multiloculated – Mirip adamantinoma

Thyroid • • • Asal : evaginasi epitel pharyngeal Normal : 15 -20 gr Hormon aktif : T 3, T 4 bebas ikatan dengan TBG

Thyroid • fungsi : – Katabolisme : - – Sintesa : - karbohidrat lemak protein

Hipertiroidisme • lab : T 3, T 4 tinggi • Gejala : - nervous lemah otot keringatan - palpitasi kurus emosionil - tremor diare capek - kulit panas tiroid besar gangguan siklus M

Hipertiroidisme Tirotoxicosis dapat karena : v v v Diffuse hiperplasi (85% Graves) hipertiroidisme Tx hormon tiroid berlebihan Multinodular goiter Neoplasma tiroid Tiroiditis

Hipertiroidisme Terjadi : 1. Hipermetabolik 2. Overaktif simpatetik

Hipertiroidisme Gejala Hipertiroid : 1. Cardiac : aritmi/palpitasi/cardiomegali 2. Otot : atrofi / fatty changes 3. Tulang : osteoporose, fraktur 4. Limfoid : hiperplasi

Hipertiroidisme 5. Ocular : Staring gaze, lid lag 6. Neuromuscular : tremor, cemas, insomnia, emosional 7. Kulit : berkeringat, rasa panas, kemerahan 8. GI : rasa haus, lapar

Hipertiroidisme Dx : Tanda klinik o Lab : o Tx : - T 4 bebas >> T S H << blocker fungsi adrenergic propil tiouracil sintesa T 3 T 4 jodium pelepasan T 3 T 4 radioactive jodium

Hipotiroidi Sebab : 1. Primer gangguan tiroid 2. Sekunder

Hipotiroidi karena parenchim tiroid : n Embrional n Radiasi n Operatif n Hashimoto

Hipotiroidi karena sintesa : n Idiopatik n Cacat sintesa turunan n Jodium intake kurang n Bahan-bahan goitrogen

Hipotiroidi karena supratiroidal : • Lesi hipofise • Lesi hipotalamus

Hashimoto Thyroiditis • Penyakit autoimmune hipotiroidi • Umur 45 -65, ♀ : ♂ = 10 -20 : 1 • Ada unsur familiar twin monozigote = 30 -60% • Sering disertai Rh, arthritis, SLE

Morfologi • Diffuse, berbatas jelas • Pucat, abu-abu, kenyal, noduler • Kapsul intak

Klinik • Struma tidak nyeri, simetrik diffuse • Kadang-kadang noduler • Hipotiroidisme, kadang-kadang hipertiroidisme transien • Risk factor timbul limfoma

Figure 24 -9 Pathogenesis of Hashimoto thyroiditis. Three proposed models for mechanism of thyrocyte destruction in Hashimoto disease. Sensitization of autoreactive CD 4+ T cells to thyroid antigens appears to be the initiating event for all three mechanisms of thyroid cell death. See the text for details. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03: 46 AM) © 2005 Elsevier

De Quervain Tiroiditis : • • • Jarang terjadi Usia 30 – 50 tahun Wanita : Pria = 3 – 5 : 1

Morfologi : • • Unilateral / bilateral Kenyal, kapsul intak Kadang-kadang perlekatan jaringan sekitar Warna kuning pucat, kecoklatan

Klinik : • Terjadi mendadak / bertahap • Nyeri leher, panas, capek, malas, anorexi, myalgin • Terdapat struma • Dapat sembuh spontan • T 3 T 4 , TSH

Figure 24 -11 Subacute thyroiditis. The thyroid parenchyma contains a chronic inflammatory infiltrate with a multinucleate giant cell (above left) and a colloid follicle (bottom right). Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03: 46 AM) © 2005 Elsevier

Graves Disease Triad yang harus ada : 1. Hipertiroidi, dengan goiter aktif 2. Ophthalmopathy exophthalmos 3. Dermatopathy pretibial myxedema

Klinik : o Usia 20 -40 tahun, wanita : pria = 7 : 1 o Ada faktor genetik

Figure 24 -8 A patient with hyperthyroidism. A wide-eyed, staring gaze, caused by overactivity of the sympathetic nervous system, is one of the features of this disorder. In Graves disease, one of the most important causes of hyperthyroidism, accumulation of loose connective tissue behind the eyeballs also adds to the protuberant appearance of the eyes. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03: 46 AM) © 2005 Elsevier

Figure 24 -12 Diffusely hyperplastic thyroid in a case of Graves disease. The follicles are lined by tall, columnar epithelium. The crowded, enlarged epithelial cells project into the lumens of the follicles. These cells actively resorb the colloid in the centers of the follicles, resulting in the scalloped appearance of the edges of the colloid. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09: 36 AM) © 2005 Elsevier

Ophthalmopathy graves • Jaringan ikat orbita Mirip TSH receptor • Otot extra ocular Ab B cell T cell, CD 4+ / CD 8+

Morfologi : • Struma, Sp 80 gr, simetri berkapsul • Konsistensi lunak, halus, merah seperti daging • Sel-sel silindris, papil-papil kecil • Colloid sedikit, dengan ‘scalloped’ margin • Infiltrasi limfosit ( B cell )

Terapi : • Jodium involusi epitel sekresi tiroglobulin turun • Propilthiouracil sintesa kurang • Radioaktif jodium • pembedahan

Neoplasma Tiroid • • Bentukan soliter, palpable Wanita : pria = 4 : 1 Sebagian besar nodul soliter jinak Nodul neoplastik 90% adenoma

Beberapa kriteria penyokong Dx • • • Nodul soliter neoplasma Usia muda neoplasma Jenis kelamin laki-laki neoplasma Pernah diterapi Rö Ca Hot nodule jinak

Adenoma tiroid • Soliter • Folikel follicular adenoma • Beberapa jenis, tersering : simple colloid adenoma • Adenoma sangat jarang menjadi Carcinoma

Figure 24 -14 Follicular adenoma of the thyroid. A solitary, well-circumscribed nodule is seen. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09: 36 AM) © 2005 Elsevier

Figure 24 -14 Follicular adenoma of the thyroid. A solitary, well-circumscribed nodule is seen. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09: 36 AM) © 2005 Elsevier

Figure 24 -14 Follicular adenoma of the thyroid. A solitary, well-circumscribed nodule is seen. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09: 36 AM) © 2005 Elsevier

Morfologi adenoma • • • Tumor soliter Bentuk speris Berkapsul, tekanan jaringan sekitar Ukuran sekitar 3 cm Warna abu-abu putih, merah kecoklatan Kadang 2 perdarahan, fibrosis, kalsifikasi, kistik

mikroskopis • Folikel ukuran sama, isi folikel • Jenis : Simple colloid (macrofolicular) Fetal (microfolicular) Embryonal (trabecular) Hurthle cell (oxiphyl, oncocyte) Atypical Adenoma with papillae (=Papillae adenoma) (=Encapsuled Papillary Ca)

Tumor Tiroid Jinak yang lain • • • Kista tiroid : deri adenoma folicular dari multinodular goiter Kista dermoid Lipoma Hemangioma Terratoma

Carcinoma Thyroid • Umumnya usia dewasa • Wanita > pria, khususnya usia muda • Terdapat reseptor estrogen pada sel-sel tumor

Jenis Carcinoma • • Papillary Ca Follicular Ca Medullary Ca Anaplastic Ca 75 -85 10 -30 5 5 % %

Papillary Carcinoma • Semua usia, terutama 20 -40 tahun • Erat hubungannya dengan fakta radiasi

Figure 24 -17 Papillary carcinoma of the thyroid. A, The macroscopic appearance of a papillary carcinoma with grossly discernible papillary structures. This particular example contains well-formed papillae (B), lined by cells with characteristic empty-appearing nuclei, sometimes termed "Orphan Annie eye" nuclei (C). D, Cells obtained by fine-needle aspiration of a papillary carcinoma. Characteristic intranuclear inclusions are visible in some of the aspirated cells. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09: 36 AM) © 2005 Elsevier

Figure 24 -17 Papillary carcinoma of the thyroid. A, The macroscopic appearance of a papillary carcinoma with grossly discernible papillary structures. This particular example contains well-formed papillae (B), lined by cells with characteristic empty-appearing nuclei, sometimes termed "Orphan Annie eye" nuclei (C). D, Cells obtained by fine-needle aspiration of a papillary carcinoma. Characteristic intranuclear inclusions are visible in some of the aspirated cells. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09: 36 AM) © 2005 Elsevier

Morfologi • Soliter atau multipel • Berbatas jelas / berkapsul / menyebar diluarnya • Kadang 2 fibrosis, kalsifikasi, kistik • Pada irisan granula / papil-papil kecil

Mikroskopis : • Papil dengan fibrovasculer, dilapisi epitel v Inti dengan ground glass / orphan annie • Intra nuclear inclusion / groves v Psammoma bodies

Klinik • Sering a symptomatic • Sering dengan metastasis kelenjar leher • Radioactive jodium cold nodule • FNA, cara Diagnosa yang tepat

Follicular Carcinoma • Wanita > Pria • Usia 40 – 50 tahun • Sering sudah didapatkan colloid goiter

Morfologi : • Single nodule • Batas jelas / infiltratif • Tumor besar infiltrasi ke jaringan sekitar • Warna abu-abu – coklat – merah muda • Kadang 2 fibrosis, kalsifikasi

Figure 24 -18 Follicular carcinoma. Cut surface of a follicular carcinoma with substantial replacement of the lobe of the thyroid. The tumor has a light-tan appearance and contains small foci of hemorrhage. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09: 36 AM) © 2005 Elsevier

Figure 24 -19 Follicular carcinoma of the thyroid. A few of the glandular lumens contain recognizable colloid. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 02: 32 PM) © 2005 Elsevier

mikroskopis : • Folikel 2 seperti normal, atau dengan diferensiasi yang rendah • Kadang 2 dengan sel Hurthle • Invasi sel pada kapsul atau vascular

Klinik : • Nodul kecil, lambat laun membesar • Rö cold nodule • Metastasis hematogen ke organ jauh

Medullary Carcinoma • Dari para follicular cell • Hormon yang dikeluarkan - Calcitonin Serotonin - CEA Somatostatin - VIP (Vasoactive Intestinal Peptide)

Figure 24 -21 Medullary carcinoma of thyroid. These tumors typically show a solid pattern of growth and do not have connective tissue capsules. (Courtesy of Dr. Joseph Corson, Brigham and Women's Hospital, Boston, MA. ) Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 02: 32 PM) © 2005 Elsevier

Figure 24 -21 Medullary carcinoma of thyroid. These tumors typically show a solid pattern of growth and do not have connective tissue capsules. (Courtesy of Dr. Joseph Corson, Brigham and Women's Hospital, Boston, MA. ) Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 02: 32 PM) © 2005 Elsevier

Morfologi • Soliter type sporadic • Multipel type familial • Jaringan tumor halus, warna abu 2 coklat • Kadang 2 nekrosis, perdarahan

Klinis • Nodul di thyroid • Kadang 2 disertai diare karena VIP • Type sporadic / MEN tumbuh agresif • Type familial low grade

Mikroskopis • Sel poligonal, spindle, dalam sarang/trabekula/folikel • Deposit amiloid ( dari molekul calcitonin)

Anaplastic Carcinoma : • Sangat agresif • Usia tua, 65 tahun • Sering didahului multinodular goiter

Morfologi : • Large, pleomorfik giant cell • Spindle cell • Small anaplastic cell

Congenital anomali Tiroid Ductus/cyst thyroglossus • Sisa 2 vestigial remnant • Lesi kecil 2 -3 cm • Letak antara Glossus - Thyroid

Parathyroid • Dari kantung pharyngeal, ada 4 kelenjar • Berat 35 -40 mg • Terdiri dari chief cell germal parathormon oxyphil cell • Kerja parathyroid dikendalikan oleh Ca ion darah

Figure 24 -24 Parathyroid adenomas are almost always solitary lesions. Technetium-99 m-sestamibi radionuclide scan demonstrates an area of increased uptake corresponding to the left inferior parathyroid gland (arrow). This patient had a parathyroid adenoma. Preoperative scintigraphy is useful in localizing and distinguishing adenomas from parathyroid hyperplasia, where more than one gland would demonstrate increased uptake. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 02: 32 PM) © 2005 Elsevier

Figure 24 -25 Parathyroid adenoma. A, Solitary chief cell parathyroid adenoma (low-power photomicrograph) revealing clear delineation from the residual gland below. B, High-power detail of a chief cell parathyroid adenoma. There is some slight variation in nuclear size but no anaplasia and some slight tendency to follicular formation. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 02: 32 PM) © 2005 Elsevier

Hormon PTH bekerja : a. Pada tulang menambah aktivitas osteoclast b. Pada ginjal meningkatkan resorbsi calcium konversi vit D aktif ekskresi phosphat c. Pada usus menambah absorbsi kalsium

Tumor 2 ganas yang lain calcium darah tinggi 1. Metastasis tulang osteolisis 2. PTH related protein ( PTH r. P )

Hiperparatiroidisme primer • Sebabnya : • Adenoma 75 -80 • Hiperplasia 10 -15 • Carcinoma 5 % % % • Usia tersering pada dewasa 50 th lebih • Wanita lebih sering dp laki-laki • Ada faktor radiasi sebelumnya

Figure 24 -26 Cardinal features of hyperparathyroidism. With routine evaluation of calcium levels in most patients, primary hyperparathyroidism is often detected at a clinically silent stage. Hypercalcemia from any other cause can also give rise to the same symptoms. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 02: 32 PM) © 2005 Elsevier

Morfologi • Tumor soliter, kecil 0, 5 – 5 gr • Lunak, batas jelas, kecoklatan • Mikroskopis : • Sel 2 poligonal, uniform • Inti kecil, central • Klinik, dapat berupa : o A symptomatic hyperparathyroidism o Symptomatic hyperparathyroidism

Pada symptomatic timbul : • Tulang osteoporosis • Ginjal nephrolithiasis • Gastrointestinal constipasi, ulcus dll • CNS depresi • Neuromuscular lemah • Cardiac kalsifikasi katup